Recognizing the public's health is the outcome of dynamic, adaptive, and complex systems of agencies; infrastructure, relationships, and interactions that dictate how to improve health outcomes; and reducing health risks in a population is based on systems thinking and evidence. New methods such as network analysis and public health practice–based research networks demonstrate the potential for new insight to our understanding of how systems and infrastructure influence population health. We examine advances in public health systems research since 1988 and discuss the relevance of this type of research to public health practice. We assess the current infrastructure for conducting public health systems research, suggest how the research infrastructure can be improved, and conclude with a discussion of how health reform in the United States will require research focused on understanding the adaptive complexity inherent in public health and health care systems and strengthening the systems research infrastructure.